Background:Current single-cell and spatial transcriptomic studies on bladder cancer tissue samples are limited, highlighting the need for advanced molecular and single-cell approaches to enhance our understanding of these complexities and identify reliable prognostic indicators. Materials and methods:We integrated and analyzed five publicly available single-cell RNA-seq datasets, totaling over 530 000 cells from 62 bladder cancer and normal samples, conducting comprehensive analyses that were validated using single-nucleus and spatial transcriptomic datasets. Additionally, spatial transcriptomics findings were confirmed through RNA fluorescence in situ hybridization. Results:Our integrated single-cell analysis uncovered stage-dependent heterogeneity in bladder cancer, with malignant epithelial cells exhibiting dynamic trajectories and enrichment in the PI3K-AKT-mTOR pathway. A distinct subcluster of malignant epithelial cells characterized by the highest basal score (C8) was identified; this subpopulation appears to be specifically regulated by RUNX3, is associated with poorer prognosis, and predominantly interacts with exhausted CD8 T cells, IL7R+ naïve T cells, and FCN1+ monocytes via the MIF-CD74 signaling pathway. Elevated pathway activity scores for both the PI3K-AKT-mTOR and MIF-CD74 pathways were observed in single-nuclei and spatial tumor tissues, with notable colocalization of key markers mainly within bladder cancer regions. Conclusion:Our study demonstrates that RUNX3+ basal-like malignant epithelial cells, along with other immunosuppressive cell subtypes, their interactions, and pathway signatures, hold promise as prognostic biomarkers. These insights may facilitate the development of personalized therapeutic strategies for bladder cancer.

Sunitinib is an important therapeutic option for renal cell carcinoma (RCC), but reduced response to sunitinib still limits its clinical benefit. This study explored the mechanism underlying reduced sunitinib sensitivity in RCC and aimed to identify potential strategies to improve sunitinib response. RCC organoids were established and characterized, and sunitinib-responsive genes were screened by transcriptomic analysis. Public datasets and clinical RCC samples were used to evaluate the clinical relevance of ALDH1L2. ALDH1L2 overexpression and knockdown were performed in RCC organoids to examine its effects on sunitinib sensitivity and ferroptosis-related changes. Organoid-derived xenograft models were used for in vivo validation. Molecular docking, cytotoxicity assays, CETSA, SPR, and functional experiments were used to screen and validate candidate compounds targeting ALDH1L2. Sunitinib inhibited RCC organoid growth, with IC50 values of approximately 8 μM. Transcriptomic analysis showed that ALDH1L2 was upregulated after sunitinib treatment. Clinical analyses indicated that ALDH1L2 was highly expressed in RCC tissues and was associated with poorer survival and advanced stage. In RCC organoids, ALDH1L2 overexpression attenuated sunitinib-induced ROS accumulation and ferroptosis-related changes, as reflected by changes in GPX4, SLC7A11, GSH/GSSG, NADP+ /NADPH, Fe2 +, and MDA. In contrast, ALDH1L2 knockdown enhanced these changes and increased the sensitivity of RCC organoids to sunitinib. In organoid-derived xenograft models, ALDH1L2 overexpression reduced the antitumor effect of sunitinib and decreased tumor ROS accumulation. Erastin counteracted the protective effect of ALDH1L2 overexpression. Hederacolchiside A1 (HA-1) was identified as a candidate compound targeting ALDH1L2. HA-1 reduced ALDH1L2 protein abundance, altered its thermal stability, enhanced the inhibitory effect of sunitinib, and counteracted ALDH1L2-mediated sunitinib tolerance in RCC organoids. These findings suggest that ALDH1L2 contributes to reduced sunitinib sensitivity in RCC organoids by attenuating ferroptosis-related responses. HA-1 may improve the response of RCC organoids to sunitinib by targeting ALDH1L2, supporting further evaluation of this combination strategy.

Background:Long non-coding RNA (lncRNA) X inactive-specific transcript (XIST) is linked to tumor metastasis; however, research on its role in renal cancer (RC) is limited. This study investigated the function and underlying mechanism of XIST in RC. Methods:After transforming growth factor beta (TGF-β) stimulation of 786-O and Caki-1 cells, morphological changes were assessed by microscopy, and XIST expression was quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). XIST-microRNA-141-3p (miR-141-3p) and miR-141-3p-zinc-finger E-box binding protein 1 (ZEB1) interactions were validated by dual-luciferase reporter assays. Cells were then transfected with small interfering (si)-XIST alone or combined with miR-141-3p inhibitor, followed by analyses of: (I) XIST and miR-141-3p expression; (II) cellular morphology; (III) proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay]; (IV) apoptosis (flow cytometry); (V) epithelial-mesenchymal transition (EMT) markers (N-cadherin, Vimentin, and Snail) and E-cadherin (western blot/immunofluorescence); and (VI) migration and invasion (Transwell assays). ZEB1-mediated rescue of miR-141-3p mimic effects was similarly examined. Results:TGF-β triggered EMT in RC cells and elevated XIST expression. XIST knockdown suppressed proliferation, EMT, migration, and invasion, while promoting apoptosis in TGF-β-stimulated cells. Mechanistically, XIST sponged miR-141-3p, and miR-141-3p inhibition partially rescued the phenotypic effects of XIST silencing. Additionally, ZEB1 was identified as a miR-141-3p target, and ZEB1 overexpression reversed the miR-141-3p mimic-mediated suppression of TGF-β-induced malignant behaviors. Conclusions:These findings establish the XIST/miR-141-3p/ZEB1 axis as a regulator of TGF-β-driven proliferation and metastasis in RC in vitro.

Several types of non-coding RNAs such as circRNAs, lncRNAs, and miRNAs have been identified to regulate mRNAs through the mechanism known as the competitive endogenous RNA (ceRNA) network. To explore the role of the ceRNA regulatory network in the immune microenvironment of bladder cancer, whole-transcriptome sequencing of bladder tumor and its peritumoral tissues from 38 bladder cancer patients, with a total of 63 samples, was performed to screen differentially expressed circ-, lnc-, mi-, and mRNAs to construct a circ/lnc-mi-mRNA regulatory network with pruning algorithms. We excavated a key immune-related gene BDNF to build the final ceRNA network as hsa-miR-107 sponged by hsa-circ-000211, AC108488.1, and LINC00163. Finally, a meta-analysis of 7 public datasets demonstrated that low expression of BDNF and high expression of hsa-miR-107 were associated with longer survival. Our study identified a ceRNA regulatory network as a potentially new prognostic marker and molecular therapeutic target of bladder cancer.

In women, stress urinary incontinence (SUI), leakage of urine from increased abdominal pressure, is correlated with pudendal nerve (PN) injury during childbirth. Expression of brain-derived neurotrophic factor (BDNF) is dysregulated in a dual nerve and muscle injury model of childbirth. We aimed to use tyrosine kinase B (TrkB), the receptor of BDNF, to bind free BDNF and inhibit spontaneous regeneration in a rat model of SUI. We hypothesized that BDNF is essential for functional recovery from the dual nerve and muscle injuries that can lead to SUI. Female Sprague–Dawley rats underwent PN crush (PNC) and vaginal distension (VD) and were implanted with osmotic pumps containing saline (Injury) or TrkB (Injury + TrkB). Sham Injury rats received sham PNC + VD. Six weeks after injury, animals underwent leak-point-pressure (LPP) testing with simultaneous external urethral sphincter (EUS) electromyography recording. The urethra was dissected for histology and immunofluorescence. LPP after injury and TrkB was significantly decreased compared to Injury rats. TrkB treatment inhibited reinnervation of neuromuscular junctions in the EUS and promoted atrophy of the EUS. These results demonstrate that BDNF is essential to neuroregeneration and reinnervation of the EUS. Treatments aimed at increasing BDNF periurethrally could promote neuroregeneration to treat SUI.

Abstract Background Despite the advances in immunotherapy for bladder cancer in recent years, the efficacy is unsatisfactory as expected. In this study, we have conducted a reliable immune-related gene prognostic index to predict immunotherapy efficacy for bladder cancer based on public databases. Methods Differential expression analysis on comparing the tumor and normal samples in the merged TCGA-BLCA & GTEx databases was applied, and the differential expressed immune-related genes were sent to Weighted gene coexpression network analysis. Multivariable Cox analysis of genes among the three most significant coexpression modules was used to develop an immune-related gene prognostic index, and the merged three GEO dataset was used as an independent validation cohort. Further, a model that combined the index with other clinicopathologic features was also verified independently. Results 11 genes were harvested to construct an immune-related gene prognostic index, both the index and clinicopathologic-index model were well verified in independent cohorts. Conclusions The immune-related gene prognostic index for bladder cancer was a reliable and useful marker to predict immunotherapy efficacy for bladder cancer.

Radioresistance of prostate cancer (PCa) is a major factor leading to local failure of radiotherapy. STAT3 is an oncogenic protein that was recently found to be activated in PCa tumors. This study aimed to investigate the radiosensitization effect of targeting STAT3 in PCa tumors. Here, the radiosensitization effect of STAT3 blockade was investigated by clonogenic assay, flow cytometry and western blot analysis in human PCa cells in vitro and in vivo. We demonstrated that STAT3 blockade with a STAT3 inhibitor or siRNA increased the radiosensitivity of PCa cells and that radiation together with STAT3 blockade induced more apoptosis and double-strand breaks (DSBs) than radiation alone in LNCaP cells. In addition, radiation induced STAT3 activation and survivin expression in PCa cells, which was inhibited by STAT3 blockade. Transfection with survivin cDNA attenuated the radiosensitization effect of STAT3 blockade. These effects were further confirmed by in vivo studies, which showed that the STAT3 inhibitor enhanced the treatment efficacy of radiation on LNCaP xenografts with decreased STAT3 activation and survivin expression. These findings suggest that STAT3 blockade radiosensitizes PCa cells through regulation of survivin. Thus, our study has revealed STAT3 as a potential sensitizer for irradiation in PCa cells. Its clinical application as an adjuvant in radiotherapy of PCa should be explored in the future.

Diabetes mellitus is a chronic metabolic disease, posing a considerable threat to global public health. Treating systemic comorbidities has been one of the greatest clinical challenges in the management of diabetes. Diabetic bladder dysfunction, characterized by detrusor overactivity during the early stage of the disease and detrusor underactivity during the late stage, is a common urological complication of diabetes. Oxidative stress is thought to trigger hyperglycaemia-dependent tissue damage in multiple organs; thus, a growing body of literature has suggested a possible link between functional changes in urothelium, muscle and the corresponding innervations. Improved understanding of the mechanisms of oxidative stress could lead to the development of novel therapeutics to restore the redox equilibrium and scavenge excessive free radicals to normalize bladder function in patients with diabetes.

CONCLUSIONS: There is considerable variability in coverage and reimbursement rates for third line therapies amongst Medicaid bene fi ciaries across different states. The variability in reimbursement and coverage may have implications on access to care in this under- served patient population.

Abstract Immunotherapy for bladder cancer is prevalent, while the efficacy is uncertain. To predict the outcomes of immunotherapy in bladder cancer patients, we had delineated the landscape of the tumor immune microenvironment based on two independent public databases, classified the bladder cancers in the training cohort as well as the validating cohort into the immune high and immune low subtypes, and identified 23 differentially expressed immune-related genes between the two subtype patients to build a prognostic gene risk score model. We further combined the model with other clinicopathologic signatures to develop a Clinical-Gene-Risk-Score (CGRS) prognosis model and validations of the two models in independent cohorts revealed good accuracy. Our model could provide prognostic indicators and potential immunotherapeutic targets for bladder cancers.

Abstract Background Immunotherapy for bladder cancer is prevalent, while the efficacy is uncertain. To predict the outcomes of immunotherapy in bladder cancer patients, an immune-related prognosis model was conducted in this study. Methods Single sample Gene Set Enrichment Analysis was used to delineate the landscape of the tumor immune microenvironment based on two independent public databases. Hierarchical clustering analysis and t-distributed Stochastic Neighbor Embedding cluster map were used to classify the bladder cancers in the training cohort as well as the validating cohort into the immune high and immune low subtypes. Differentially expression analysis and The least absolute shrinkage and selection operator regression analysis had identified 23 differentially expressed immune-related genes between the two subtype patients to build a prognostic gene risk score model. Further combining the model with other clinicopathologic signatures, a Clinical-Gene-Risk-Score (CGRS) prognosis model was developed. Results Validations of the two models in independent cohorts revealed good accuracy. Conclusions Our model could provide prognostic indicators and potential immunotherapeutic targets for bladder cancers.

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (PD27)1 Sep 2021PD27-02 WIRELESS CATHETER-FREE AMBULATORY URODYNAMICS FOR BLADDER PHYSIOLOGY RESEARCH Maxx Caveney, Steve Majerus, Kangli Deng, Brett Hanzlicek, Binit Panda, James Mrowca, Dennis Bourbeau, and Margot Damaser Maxx CaveneyMaxx Caveney More articles by this author , Steve MajerusSteve Majerus More articles by this author , Kangli DengKangli Deng More articles by this author , Brett HanzlicekBrett Hanzlicek More articles by this author , Binit PandaBinit Panda More articles by this author , James MrowcaJames Mrowca More articles by this author , Dennis BourbeauDennis Bourbeau More articles by this author , and Margot DamaserMargot Damaser More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002020.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: As with clinical urodynamics, investigations into lower urinary tract physiology using animal models require catheter-based systems to measure bladder pressure while filling the bladder, often under anesthesia. However, anesthesia, catheters and filling of the bladder can affect filling pressures, urinary leakage and voiding reflexes. To enable recordings more representative of normal physiology, we developed a catheter-free, wireless, intravesical sensor which is implanted in the feline bladder lumen and wirelessly transmits bladder pressure and volume data. We validated sensor function by recording volume and pressure over 4-week implantations in felines. METHODS: The Urological Monitor of Conscious Activity (UroMOCA) measures 18x12x5.6 mm and wirelessly transmits data to a radio and antenna placed in an animal backpack. The UroMOCA battery can be recharged wirelessly via a charging mat placed under the subject. Platinum electrodes measuring urine concentration and conductance estimate urine volume and are paired with an onboard pressure sensor. Under anesthesia, a UroMOCA was implanted into the bladder lumen via cystotomy in male felines. Baseline cystometry was performed and CT imaged the UroMOCA in the bladder. Anesthetized cystometry with UroMOCA recording and imaging were repeated 2 and 4 weeks post-implantation. Ambulatory recordings were performed multiple times for up to two hours per session during the four weeks prior to device explantation. Sham surgeries and sham devices were implanted in some animals to assess the impact of the UroMOCA on the bladder. RESULTS: 10 feline cats were enrolled: 3 were sham implants (no device), 1 received an inactive device, and 6 received a functional UroMOCA. Non-anesthetized recordings were performed for a total 2,899 minutes over 33 ambulatory sessions. After 2 weeks, all animals resumed normal voiding volume. Urinary retention requiring intermittent catheterization was seen in 1 feline; there was no evidence of obstruction. Wireless pressure data linearly correlated with anesthetized cystometry (R2=0.96). Volume measurement was variable but decreased during voiding and increased during filling. Histology showed normal bladder tissue. CONCLUSIONS: A small, wireless, catheter-free, intravesical sensor enabled conscious recordings of bladder function in felines during natural bladder filling over 4 weeks. The volume sensor enabled differentiation of an empty from a full bladder. Source of Funding: This work was funded by the NIH Stimulating Peripheral Activity to Relieve Conditions (SPARC) program, NIH grant number OT2OD023873 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e443-e444 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Maxx Caveney More articles by this author Steve Majerus More articles by this author Kangli Deng More articles by this author Brett Hanzlicek More articles by this author Binit Panda More articles by this author James Mrowca More articles by this author Dennis Bourbeau More articles by this author Margot Damaser More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II (MP52)1 Sep 2021MP52-10 CLINICAL STUDY OF A NEUROMODULATIVE SLING SYSTEM WITH TVT-XO PROCEDURE IN THE TREATMENT OF MIXED URINARY INCONTINENCE Hai-Hong Jiang, Xiao-Liang Zhu, Yasmeen Bano, Qi-Xiang Song, Kang-Li Deng, Jiahui Liu, Hongbing Liao, and Meihao Wang Hai-Hong JiangHai-Hong Jiang More articles by this author , Xiao-Liang ZhuXiao-Liang Zhu More articles by this author , Yasmeen BanoYasmeen Bano More articles by this author , Qi-Xiang SongQi-Xiang Song More articles by this author , Kang-Li DengKang-Li Deng More articles by this author , Jiahui LiuJiahui Liu More articles by this author , Hongbing LiaoHongbing Liao More articles by this author , and Meihao WangMeihao Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002082.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Mixed urinary incontinence (MUI) is a relatively complex medical condition. To evaluate the safety and effectiveness of the neuromodulative sling system with TVT-XO procedure in MUI, we performed surgical treatment and short-term observation on 11 women with severe MUI by using a new neuromodulative sling system combined with a new anti-incontinence TVT-XO suspension procedure. METHODS: A total of 11 adult female patients with severe MUI were included under the following screening criteria: leakage point pressure < 60 cm H2O, severe bladder urgent symptoms (overactive bladder symptom score(OABSS) >12), and no significant improvement after pelvic floor exercise and related medications. The principle of TVT-XO suspension is that two sling tapes crossover stereoscopic suspension of the urethra. The microelectric stimulating lead along the shell of the left suprapubic sling was inserted below the middle and proximal suburethral urethra. The stimulator was then attached to the lead. During neuromodulation after implantation, the urgency can be regulated through feedback. RESULTS: All 11 patients underwent TVT-XO procedure along with the neuomodulative sling system implantation successfully. With neuromodulation treatment one month after surgery, it indicated significant improvements in MUI symptoms, including the short version of questionnaire IIQ7 and the OABSS score (p < 0.05). CONCLUSIONS: Our preliminary study demonstrated the TVT-XO sling procedure along with a new neuromodulative sling can simultaneously improve patients' urinary incontinence and urgency with no serious complications. The limitations of the study include the small number of patients and the short time of the observation. We expected a large-scale trial and long-term observation of the safety and effectiveness. Source of Funding: Zhejiang Provincial Natural Science Foundation of China (No. WY20H050001), Zhejiang Provincial Medical and Health Technology Program projects of China (Nos. 2018PY031, 2018KY512, and 2019KY101), and National Natural Science Foundation of China (No. 81670695) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e933-e933 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hai-Hong Jiang More articles by this author Xiao-Liang Zhu More articles by this author Yasmeen Bano More articles by this author Qi-Xiang Song More articles by this author Kang-Li Deng More articles by this author Jiahui Liu More articles by this author Hongbing Liao More articles by this author Meihao Wang More articles by this author Expand All Advertisement PDF downloadLoading ...

Nonmuscle invasive bladder cancer (NMIBC) is mainly composed of three different types of tumors: papillary urothelial carcinoma is limited to the mucosal layer (Ta), high-grade carcinoma in situ is limited to the epithelial layer (CIS) and tumors invading the submucosa or lamina propria (T1). The standard treatment for NMIBC is complete transurethral resection of bladder tumors (TURBT) with or without intravesical instillation therapies. However, some high-risk patients are at risk of tumor progression and therefore require more aggressive treatment. Studies have reported that delayed cystectomy can lead to a significant reduction in survival benefits. Therefore, for these NMIBC patients who are at high risk of disease progression, when to abandon conservative treatment and choose cystectomy is one of the biggest challenges. This article reviews the current application status and future directions of radical cystectomy as the initial treatment on NMIBC patients.

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II (MP52)1 Sep 2021MP52-06 STEM CELL SECRETOME ACCELERATES RECOVERY FROM STRESS URINARY INCONTINENCE Brian Balog, Kangli Deng, Mei Kuang, Anna Rietsch, Katelyn Woolley, Martin Cramer, Michael Coleman, and Margot Damaser Brian BalogBrian Balog More articles by this author , Kangli DengKangli Deng More articles by this author , Mei KuangMei Kuang More articles by this author , Anna RietschAnna Rietsch More articles by this author , Katelyn WoolleyKatelyn Woolley More articles by this author , Martin CramerMartin Cramer More articles by this author , Michael ColemanMichael Coleman More articles by this author , and Margot DamaserMargot Damaser More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002082.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Stress Urinary Incontinence (SUI) is common among older women. We have shown that secretome of rat mesenchymal stem cells (MSC) improves SUI in a rat model. To translate this work, a human cell source is needed and the manufacturing method must be adaptable to current good manufacturing practice (cGMP). The aim of this study was to use an SUI rat model to compare treatment with human adipose-derived stem cell secretome (hASC) prepared using cGMP compliant method to the rat MSC secretome manufactured by lab method (rMSC) and using the cGMP compliant process (rGMP). METHODS: Concentrated hASC secretome (100-fold) was prepared from single donor female human adipose-derived stem cells at passages 7-9. Concentrated rMSC and rGMP secretome (50 or 100-fold, respectively) were prepared from passage 11-13 rat Sprague-Dawley MSCs. 54 Female Sprague-Dawley rats were divided into 5 groups: 1) sham injured rats with sham treatment (control media); 2) SUI rats with pudendal nerve crush (PNC) & vaginal distension (VD) & sham treatment; 3) SUI + rMSC rats with PNC&VD & rMSC secretome treatment; 4) SUI + rGMP rats with PNC&VD & rGMP secretome; 5) SUI + hASC rats with PNC&VD & hASC secretome. Treatments consisted of a single dose of 300 µl given intraperitoneally 1 hour after the end of VD. Three weeks after injury and treatment, animals underwent functional testing: leak point pressure (LPP) with external urethral sphincter electromyography (EUS EMG), followed by pudendal nerve sensory branch recordings. Urethras were harvested to evaluate neuromuscular junction (NMJ) innervation. Data are presented as mean ± SEM for 10-11 rats in each group. ANOVA on ranks followed by Dunns posthoc test with p<0.05 compared data. RESULTS: All 3 treatments (rMSC: 36.9 +/- 2.7 cmH2O, hASC: 35.3 +/- 1.4 cmH2O, rGMP: 34.5 +/- 1.4 cmH2O) significantly increased LPP compared to the SUI group (18.1 +/- 2.7 cmH2O). hASC (1003.9 +/- 150.7 Hz.) and rMSC treatments (991.1 +/- 234.8 Hz.) significantly increased EUS EMG firing rate compared to the SUI group (217.0 +/- 107.5 Hz.). hASC (792.0 +/- 110.7 Hz) and rGMP treatments (716.6 +/- 165.9 Hz) significantly increased nerve firing rate compared to the SUI group (156.3 +/- 68.4 Hz). NMJ staining from hASC and rGMP groups showed improved reinnervation compared to the SUI group. CONCLUSIONS: All stem cell secretome treatments accelerated recovery of the continence mechanism. Specific differences in outcomes between rMSC and rGMP treatments suggest that manufacturing method affects secretome activity. Results support secretome as a possible therapeutic for SUI. Source of Funding: NIH R41 DK122904 and Theratome Bio, who did not participate in data collection or analysis. Conflict of Interest: Theratome Bio has an option to license Dr. Damaser’s IP which is relevant to this project. Drs. Coleman and Cramer are employees of Theratome Bio. No other authors have a COI © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e932-e932 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brian Balog More articles by this author Kangli Deng More articles by this author Mei Kuang More articles by this author Anna Rietsch More articles by this author Katelyn Woolley More articles by this author Martin Cramer More articles by this author Michael Coleman More articles by this author Margot Damaser More articles by this author Expand All Advertisement PDF downloadLoading ...

Transurethral and suprapubic catheterization have both been used to test urethral function in rats; however, it is unknown whether these methods affect urethral function or if the order of catheterization affects the results. The aim of this cross-over designed experiment was to compare the effects of catheterization methods and order on leak point pressure (LPP) testing. LPP and simultaneous external urethral sphincter electromyography (EUS EMG) were recorded in anesthetized female virgin Sprague-Dawley rats in a cross-over design to test the effects of transurethral and suprapubic catheterization. There was no significant difference in peak bladder pressure during LPP testing whether measured with a transurethral or suprapubic catheter. There was no significant difference in peak bladder pressure between the first and second catheter insertions. However, peak EMG firing rate, as well as peak EMG amplitude and EMG amplitude difference between peak and baseline were significantly higher after the first catheter insertion compared to the second insertion, regardless of the catheter method. Our results suggest that route of catheterization does not alter urethral function, e.g. create a functional partial outlet obstruction. Either catheterization method could be used for LPP and/or EUS EMG testing in rats.

Objective: Stress urinary incontinence (SUI) is prevalent among older women and can result from insufficient regeneration of the pudendal nerve (PN). Electrical stimulation (ES) of the PN upregulates brain derived neurotrophic factor (BDNF) and accelerates regeneration. Using tyrosine kinase B (TrkB) to reduce the availability of free BDNF, the aim of this study was to determine if BDNF is necessary for accelerated recovery via ES in a model of SUI. Methods: Our SUI model consists of Female Sprague-Dawley rats, whose PNs were crushed bilaterally twice for 30 s, followed by insertion of a modified Foley catheter into the vagina with balloon inflation for 4 h. These rats were divided into 4 groups: 1) Sham PN crush and sham vaginal distension without electrode implantation and with saline treatment (sham injury); 2) SUI with sham stimulation and saline treatment (SUI); 3) SUI and ES with saline treatment (SUI & ES); and 4) SUI and ES with TrkB treatment (SUI&ES&TrkB). Animals underwent ES or sham stimulation four times a week for two weeks. Four weeks after injury, animals underwent functional testing consisting of leak point pressure (LPP) with simultaneous external urethral sphincter (EUS) electromyography (EMG) and pudendal nerve recordings. Data was analyzed using ANOVA with Holm-Sidak posthoc test (p < 0.05). EUS and PN specimen were sectioned and stained to semi-quantitatively evaluate morphology, regeneration, and reinnervation. Results: LPP and EUS EMG firing rate were significantly increased in the sham injury and SUI&ES groups compared to the SUI and SUI&ES&TrkB groups. EUS of SUI rats showed few innervated neuromuscular junctions compared to sham injured rats, while both treatment groups showed an increase in reinnervated neuromuscular junctions. Conclusion: ES accelerates functional recovery via a BDNF-mediated pathway in a model of SUI. These findings suggest ES could be used as a potential regenerative therapy for women with SUI.

Introduction and ObjectiveThe neural control of bowel function during content storage, motility, and defecation is not well understood. A more complete understanding may be possible with electrophysiology or pharmacology studies that include functional measures of the bowel in conscious subjects. To overcome this, we developed a wireless colonic pressure and volume monitoring sensor for use anaesthetized pigs. This study validated sensor function and physiologic outcomes in 2 acute animal studies.MethodsThe device measured 80 mm long and 7 mm wide and consisted of a flexible printed circuit board housed in a silicone‐gel filled, thin‐walled silicone tube to maintain flexibility when implanted in the colon. The fully packaged device contained 5 sensors: two pressure sensors to measure circumferential and longitudinal bowel contractions, and three ring electrodes to measure conductance and conductivity of bowel contents near the device. An additional ring electrode was used as a common return for the 3 ring electrodes. The device transmitted radio data at 10 Hz and included an inductive energy interface antenna for battery recharging.Accuracy and precision of sensors were first characterized through benchtop testing in a benchtop colon phantom against a reference pressure sensor, and with artificial stools of varying water content. The functionality of the sensors was further evaluated in 2 preliminary acute in vivo experiments with the device powered through a power source.Yorkshire pigs, approximately 4–5 months old, weighing 40–60 kg were used for the in vivo experiment. Each pig was anaesthetized and the sensor was affixed to the rectum first and then to the colon using a mucosal clip. Recording was done for 5 hours and data was transmitted wirelessly to the recording device. Artificial stool of different saline concentration was inserted into the rectum to simulate different conductivity and conductance of the stool. Artificial stool was also mixed with radio contrast to take CT images of the stool location.ResultsPower consumed by the device was 140 μA when on and 2 μA when off, with an expected battery lifetime between charges of 40 hours. Benchtop results showed that the pressure sensors detected controlled pressure changes with a root mean square error (RMSE) of 3.7 cmH20. Regression analysis for the conductivity measurements showed a maximum error of 19% and a RMSE of 675 μS/cm. For volume estimation, there was a maximum error of 26% and a RMSE of 4.5 mm for the diameter of a stool. In vivo conductivity measurements were qualitatively sensitive to stools with different conductivities, and to increasing stool volume. The pressure sensors recorded changes in bowel pressure in response to abdominal compressions and slow‐wave bowel contractions.ConclusionSmall wireless, bowel sensors can help us understand the physiologic functions of the bowel and its connection with the nervous system. Initial testing indicated the feasibility of this device in pigs in measuring pressure and volume inside the bowel.Support or Funding InformationThis work was funded by the NIH Stimulating Peripheral Activity to Relieve Conditions (SPARC) program, NIH grant number OT2OD023873.